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Updated: Aug 4, 2026
Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
Integrative Transcriptomic Network Analysis of Butyrate Treated Colorectal Cancer Cells
Saira R Ali1, Ayla Orang1, Shashikanth Marri1
1Flinders Health and Medical Research Institute-Cancer Program, Flinders University, Bedford Park, SA 5042, Australia.
Abstract:
Diet-derived histone deacetylase inhibitor (HDACi), butyrate, alters global acetylation and consequently global gene expression in colorectal cancer (CRC) cells to exert its anticancer effects. Aberrant microRNA (miRNA) expression contributes to CRC development and progression. Butyrate-mediated modulation of microRNA (miRNA) expression remains under-investigated. This study employed a systems biology approach to gain a comprehensive understanding of the complex miRNA-mRNA interactions contributing to the butyrate response in CRC cells. Next-generation sequencing, gene ontology (GO) and pathway enrichment analyses were utilized to reveal the extent of butyrate-mediated gene regulation in CRC cells. Changes in cell proliferation, apoptosis, the cell cycle and gene expression induced by miRNAs and target gene knockdown in CRC cells were assessed. Butyrate induced differential expression of 113 miRNAs and 2447 protein-coding genes in HCT116 cells. Butyrate also altered transcript splicing of 1591 protein-coding genes. GO, and pathway enrichment analyses revealed the cell cycle to be a central target of the butyrate response. Two butyrate-induced miRNAs, miR-139 and miR-542, acted cooperatively with butyrate to induce apoptosis and reduce CRC cell proliferation by regulating target genes, including cell cycle-related EIF4G2 and BIRC5. EIF4G2 RNA interference mimicked the miR-139-mediated reduction in cell proliferation. The cell cycle is a critical pathway involved in the butyrate response of CRC cells. These findings reveal novel roles for miRNAs in the cell cycle-related, anticancer effects of butyrate in CRC cells.
Insights
Butyrate, a diet-derived histone deacetylase inhibitor, modulates microRNA (miRNA) expression in colorectal cancer (CRC) cells. This study reveals novel roles for specific miRNAs in butyrate
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Aberrant microRNA (miRNA) expression is implicated in colorectal cancer (CRC) development.
- Butyrate, a histone deacetylase inhibitor (HDACi) from diet, exhibits anticancer effects in CRC cells.
- The impact of butyrate on miRNA expression in CRC remains largely unexplored.
Purpose of the Study:
- To investigate the complex interplay between butyrate and miRNA-mRNA interactions in CRC cells.
- To elucidate the role of specific miRNAs in mediating the anticancer effects of butyrate.
- To understand how butyrate-induced miRNA changes influence CRC cell behavior.
Main Methods:
- Systems biology approach integrating next-generation sequencing.
- Gene Ontology (GO) and pathway enrichment analyses.
- Assessment of cell proliferation, apoptosis, cell cycle, and gene expression changes following miRNA and target gene modulation.
Main Results:
- Butyrate induced differential expression of 113 miRNAs and 2447 protein-coding genes in HCT116 CRC cells.
- The cell cycle was identified as a central pathway affected by butyrate.
- Two miRNAs, miR-139 and miR-542, cooperated with butyrate to induce apoptosis and inhibit proliferation by targeting cell cycle genes like EIF4G2 and BIRC5.
Conclusions:
- The cell cycle is a critical target pathway for butyrate's anticancer effects in CRC.
- Novel roles for specific miRNAs (miR-139, miR-542) in mediating butyrate's antiproliferative and pro-apoptotic actions were identified.
- These findings highlight the significance of miRNA-mRNA interactions in the therapeutic potential of butyrate for colorectal cancer.
